Dysproliferative diseases including neoplasms such as cancer remain a major health problem accounting for significant morbidity and mortality in the US and nearly all of the rest of the world. Despite substantial progress in the last two decades, there remain many cancers for which currently available methods are either partially or totally ineffective. Thus novel agents or methods are needed either to prevent the development of cancer, or, in the case where neoplasia has already developed, to render the host organism cancer-free or to reduce its neoplastic burden to a level compatible with life or at least to facilitate the use of concomitant therapies.
There has been significant progress in understanding the fundamental processes underlying the development of neoplasia. In its essence, neoplasia, including cancer, can be viewed as the inappropriate accumulation of cells, in violation of the exquisite balance between cell renewal and cell death. For neoplasia to develop, either cell renewal must be increased or cell death decreased or both. A corollary to this relationship is that an agent that affects these processes favorably for the host organism (and, consequently, unfavorably for the neoplasm), is a potential antineoplastic drug.
One approach to develop new antineoplastic agents is to synthesize novel chemical compounds and screen them for their effect on cell growth. This is achieved by determining the number of a given set of cells following their exposure to the agent under evaluation and comparing it to that of untreated control cells. For an agent to have antineoplastic properties, it must inhibit the growth of neoplastic cells compared to untreated control, so that its sustained or repeated application will progressively diminish the tumor mass, ultimately leading to the extinction of neoplasia. It is also a logical extension of these considerations that other diseases such as, for example, psoriasis in which cell kinetic abnormalities, in other words abnormalities in cell renewal or cell death, contribute to their pathogenesis, will be amenable to treatment by such agents.
It is toward the identification of novel compounds with antineoplastic properties, and the identification of unexpected antineoplastic activity in compounds otherwise known in the art, that the present application is directed.
All citations in the present application are incorporated herein by reference in their entireties. The citation of any reference herein should not be construed as an admission that such reference is available as “Prior Art” to the instant application.